The research proposed is designed to determine the chemical mechanisms of actions of pituitary-adrenal hormones on the brain. The chemical responses to corticotropin (ACTH) and corticosterone will be related to the specific behavioral effects of the hormones. These responses will be compared to those that occur following stress, to assess the extent to which the hormones mediate the neurochemical responses to stress. Particular emphasis will be placed on the relationships between the pituitary-adrenal response to stress and that of the catecholaminergic systems. A deoxyglucose uptake procedure will be used to identify regions of the brain whose activity is altered by stress or ACTH. Catecholamine responses to stress and pituitary-adrenal hormones will be investigated by the synthesis of catecholamines from (3H)tyrosine by brain slices in vitro, by the production of catecholamine catabolites in vivo, and by the assay of enzymes such as tyrosine hydroxylase and dopamine-Beta-hydroxylase. Similar experiments are proposed for serotonin. Serotonin synthesis from (3H)typtophan will be studied in slices following stress, ACTH and corticosterone. Also, the production of 5-hydoxyindoleacetic acid in vivo, and the activity of tryptophan hydroxylase will be assayed. Finally, we shall investigate the neural mechanisms of excessive grooming, a behavior observed following intracerebral administration of ACTH and Beta-endorphin. Grooming also occurs following stressful treatments, perhaps because of intracerebral release of ACTH. Methods to be used include deoxyglucose uptake, specific drugs and specific drug-induced lesions. The significance of these studies will be in elucidating the mechanisms of the stress response, and how hormones released during stress interact with the brain, to elicit behavior. These factors may be important in the treatment of stress, which frequently precipitates mental illness.